Results of treatment of cancer of the cervix at Addenbrooke's Hospital, Cambridge, 1946-70.
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Biomedical subjects
Publications and source records attributed to J S Mitchell.
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Enzymes involved in catecholamine metabolism were assayed in the presence of a new class of naturally occurring tetrahydroisoquinoline alkaloids, the norlaudanosolinecarboxylic acids (NLCAs). NLCAs inhibited tyrosine hydroxylase noncompetitively with respect to its substrate, tyrosine and the cofactor, 6-methyltetrahydropterin (NLCA Kj = 4 x 10(-4) M; 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) Kj = 1.5 x 10(-4) M). Adrenal dopamine-beta-hydroxylase was also inhibited by NLCAs [3'O-methylnorlaudanosolinecarboxylic acid (MNLCA) Kj = 1.2 x 10(-4) M] and NLCA is a competitive inhibitor of norepinephrine methylation by hepatic catechol-O-methyltransferase (NLCA Kj = 5.6 x 10(-5) M). While a slight reduction of rat adrenal monoamine oxidase by MNLCA was also observed, NLCA did not affect the oxidation of tyrosine by D-amino acid oxidase. Kinetic patterns of tyrosine aminotransferase and aromatic amono acid decarboxylase from rat liver were not altered by addition of 1 to 10 x 10(-5) M NLCA or its 3'-O-methyl ether (MNLCA). In vivo studies of brain tyrosine metabolism in mouse neonates corroborated results on the in vitro effect of DNLCA on tyrosine hydroxylase. The potential of high-pressure liquid chromatography was demonstrated in both enzyme assays and radiometric studies of in vivo metabolism.
Eleven hundred rats with tumours were administered vitamin B6 (pyridoxine or pyridoxal-5-phosphate) before a single local irradiation of 10 Gy. No difference in the survival rate was found in comparison with control animals. Thus vitamin B6 in the dose used afforded no significant protection against local radiation in rats. The 24-hour-xanthurenic acid excretion in urine increased with growth of the tumor and was further elevated by local radiation (10 Gy). Radiation as well as the tumour itself induce in the rat metabolic changes typical of vitamin B6 deficiency.
A simple manual after-loading system for the treatment of carcinoma of the cervix has been developed. Radiochemical Centre J-type caesium sources are used made up in PVC tubes which can be inserted into PVC uterine tubes or rubber ovoids after these have been packed in position in the patient. Radiation exposure to theatre staff has been reduced by a factor of about four.
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An attempt has been made to develop tritiated derivatives of Synkavit (menadiol sodium diphosphate, MNDP) of high specific activity as a radioactive drug.This paper summarizes the preliminary biological and physical studies, with emphasis on approximate radiation dosimetry and the necessary preliminary testing, and then gives an account of the clinical investigations and the trials carried out so far, which correspond essentially to Phases I and II trials for a chemotherapeutic agent.In all, 214 patients with different sites and types of advanced and recurrent, inoperable, histologically verified malignant tumours including reticuloses have been treated with doses of at least 1 Ci of the various preparations. Among the 203 evaluable treated cases, some form of response was observed in 23 out of 151 (15·2%) receiving the drug by intravenous injections and 13 out of 52 (25%) after intra-arterial injections. For the sites and types of malignant diseases which showed responses after either intravenous or intra-arterial administration among the 55 patients surviving at least 3 months after the first injection, some form of response was observed in 32 but only 5 of these showed either a "complete" or a "partial" response.It is concluded that further investigation is desirable. It is suggested that clinical trials with randomization should be carried out for inoperable cases of carcinoma of the colon and of the pancreas.
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